Histology of the Digestive Tube PDF

Foundations of Renal, Endocrine, and Gastro-Intestinal Medicine Histology of the Digestive Tube February 3, 2025  Foundations of Renal, Endocrine, and Gastro-Intestinal Medicine Histology of the Digestive tube This is the material students are responsible for: CBFM Lect...

Foundations of Renal, Endocrine, and Gastro-Intestinal Medicine Histology of the Digestive Tube February 3, 2025  Foundations of Renal, Endocrine, and Gastro-Intestinal Medicine Histology of the Digestive tube This is the material students are responsible for: CBFM Lectures Histology of Epithelium Histology of Integument REGI Lectures Foregut Midgut and Hindgut 2. Reading assignments necessary to comprehend topics discussed in the lecture (online available via PCOM library): Chapters 16 & 17 of Pawlina, Histology: A Text and Atlas 8th ed. Chapter 15 of Junquiera’s, Basic Histology, 15th ed. Histology of the Digestive Tube Learning Objectives: 1. Describe the general features and function of the papillae of the tongue 2. Identify the cells comprising the taste buds and list the functions of these cells 3. Identify the histological layers of the esophagus 4. Describe the general features of each of the layers of the GI tract from mouth to anus. 5. Identify the histological regions of the gastric gland and list the cells types associated with these regions 6. Identify the location and functions of each of the gastric glands (e.g. fundic, cardiac and pyloric) 7. List the cell types in the fundic glands of the stomach 8. List the functions of the parietal, chief and enteroendocrine cells 9. Describe pernicious anemia and peptic ulcers, list the common causes of the disease Histology of the Digestive Tube Learning Objectives: 10. Describe the absorptive surfaces of the small intestine 11. List the functions of the enterocytes, goblet cells, M cells and paneth cells of small intestine 12. Describe the features of the goblet cell 13. Describe the functions of cell types in the large intestinal mucosa 14. Identify the histological features of the crypts of Lieberkühn in the small and large intestines 15. Describe submuscosal structures (e.g., Brunner’s glands, Peyer’s patches) 16. Describe the role of Meissner's and Auerbach plexuses and their relationship to the innervation of the muscularis mucosa and muscularis externa Gastrointestinal system The lumen of the alimentary canal (Digestive tube) is physically and functionally external to the body. Junqueira’s Basic Histology Digestive/Gastrointestinal system Function Physical barrier pathogenic organisms, noxious substances, antigens H&E ×380 Immunologic protection lymphatic tissue/cells H&E ×120 Secretion digestive enzymes, hydrochloric acid, mucin, etc. H&E ×22 Absorption water, nutrients, vitamins, cholesterol, electrolytes, etc. H&E ×140 Digestive tube (oral cavity → anus) is a layered organ 1- Mucosa 1- Mucosa in contact with lumen barrier epithelium absorption lamina propria secretion muscularis mucosa immunologic protection 2- Submucosa 2- Submucosa immunologic protection secretion 3- Muscle (or bone – oral cavity) 3- Muscle regulate movement of luminal contents  Stratum superficiale doi.org/10.1016/j.trsl.2021.06.003 Lip Junqueira’s Basic Histology, H&E, 10x Oral cavity mucosa Lining Masticatory H&E ×380 Lining mucosa - lips, cheeks, alveolar, floor of mouth, inferior surface of tongue, soft palate Masticatory mucosa - gums (gingiva), hard palate Specialized mucosa - dorsal surface of tongue Oral cavity : Lining mucosa H&E ×380 Mucosa – epithelium, lamina propria (sensory receptors, nerves, vessels), no muscularis mucosae Submucosa – minor salivary glands, larger nerves & vessels Bone or skeletal muscle Oral cavity epithelium Lining mucosa ~nonkeratinized stratified squamous epithelium ~parakeratinized stratified squamous epithelium Masticatory mucosa ~keratinized stratified squamous epithelium ~parakeratinized stratified Pawlina, Histology: A Text and Atlas H&E ×380 squamous epithelium (nuclei kept) Specialized mucosa ~stratified squamous epithelium ~papillae (filiform – highly keratinized; fungiform – thin keratinized; foliate – nonkeratinized; circumvallate – thin keratinized)  Oral cavity : Specialized mucosa Mucosa - epithelium (taste sensory receptors) - lamina propria/connective tissue (nerves, vessels) Skeletal muscle – striated bundles run in 3 planes, minor salivary glands, larger nerves & vessels Tongue Specialized mucosa - dorsal surface of tongue Junqueira’s Basic Histology; All H&E stain Tongue - papillae Ross & Pawlina, Histology: A Text and Atlas; H&E; a-c x45, d x25  Tongue : Taste buds Neuroepithelial (sensory) cells (NSC) -Chemosensation -apical microvilli, tight junctions -synapse with cranial nerve (7,9, or 10) -turnover ~ every 10days Supporting cells (SC) -apical microvilli, tight junctions -turnover ~ every 10days Basal cells (stem cells) near basal lamina, generate sensory and supporting cells C – cleft Ep – epithelium NF – nerve fibers SE – stratified nonkeratinized epithelium TP – taste pore Ross & Pawlina, Histology: A Text and Atlas;1100x, H&E Tonsils Aggregations of lymphatic nodules Palatine (tonsils), Tubal, Pharyngeal (adenoid), and Lingual Lymphatic tissue covered by stratified squamous epithelium (SSE) that dips into underlying connective tissue forming tonsillar crypt Ross & Pawlina, Histology: A Text and Atlas; H&E. left image x25, right image x450 GI tract : Layered structural organization Mucosa Epithelium Lamina propria Muscularis mucosae Submucosa Dense irregular connective tissue, vessels (blood, lymph), glands, nerve plexus (submucosal), etc. Muscularis externa Inner circular layer Nerve plexus (myenteric) Outer longitudinal layer Serosa/Adventitia Epithelium and connective tissue  Esophagus → Large Intestine : Ross & Pawlina, What is conserved? Histology: A Text and Atlas What is different?  Enteric nervous system Myenteric (Auerbach’s) plexus Submucosal (Meissner’s) plexus FIGURE 5.51 – innervation of small intestine Enteric nervous system: Myenteric (Auerbach’s) plexus Enteric nervous system: Submucosal (Meissner’s) plexus mucosa submucosa Black arrows - ganglion cells White arrows - submucosal nerves Pathology Outlines, H&E Esophagus Ross & Pawlina, Histology: A Text and Atlas; 8x, H&E  Esophagus : Mucosa layer x10 Junqueira’s Basic Histology; H&E Nonkeratinized stratified squamous epithelium Ross & Pawlina, Histology: A Lamina propria Text and Atlas; 240x, H&E - Loose connective tissue - Diffuse lymphatic tissue & lymphatic nodules, small blood vessels - Esophageal cardiac glands, secrete neutral mucus, found in distal esophagus Muscularis mucosae - 2 layers smooth muscle (inner circular, outer longitudinal) Esophagus : Submucosa layer Dense irregular connective tissue Submucosal plexus (nerve fibers, ganglion cells), blood and lymphatic vessels Diffuse lymphatic tissue & lymphatic nodules Submucosal glands (Esophageal glands proper) - secrete slightly acidic and viscous mucus via excretory duct to lubricate luminal wall - small, compound, tubuloalveolar glands - scattered along length but more concentrated in upper half of the esophagus Pawlina, Histology: A Text and Atlas; 110x, mucicarmine Esophagus : Muscularis externa layer Inner circular muscle Superior (upper) esophageal sphincter (Pharyngoesophageal sphincter) - prevents the entry of air into the esophagus Inferior (lower) esophageal sphincter - at junction with stomach - prevents reflux of gastric contents into the esophagus Outer longitudinal muscle Upper 1/3 = striated muscle (skeletal) Middle 1/3 = striated and smooth muscle mixed Distal 1/3 = smooth muscle Myenteric plexus (nerve fibers, ganglion cells) Striated muscle – vagus nerve somatic motor neurons (nucleus ambiguus) Smooth muscle – vagus nerve visceral motor neurons (dorsal motor nucleus of X)  Esophagus → Stomach Stratified squamous epithelium → Simple columnar epithelium Junqueira’s Basic Histology; H&E x60 Clinical application : GERD – Barrett’s esophagus Esophageal Stratified squamous epithelium becomes Simple columnar epithelium  Stomach 3 histological regions –cardiac, pyloric, fundic (gland type in mucosa) Rugae – longitudinal gastric folds/ridges of mucosa & underlying submucosa Ross & Pawlina, Histology: A Text and Atlas  Stomach Muscularis externa: 3 layers - outer longitudinal, circular, inner oblique Pyloric sphincter in circular layer - controls the release of chime into duodenum Myenteric plexus Submucosa: dense connective tissue, blood vessels, adipose, nerve fibers, ganglion cells (submucosal plexus) Junqueira’s Basic Histology; H&E, x12 variable width due to rugae Stomach : Mucosa Simple columnar epithelium -forms simple tubular glands Cardiac gland – produce primarily mucus Body/Fundus gland– produce HCl & enzymes Pyloric gland – produce primarily mucus Very little lamina propria Muscularis mucosae – 2 thin layers (inner circular, outer longitudinal)  Fundic glands (Gastric glands) -Simple, branched tubular gland in mucosa -Present throughout stomach (except small areas where cardiac and pyloric glands are located) 3 regions to gland: Isthmus (stem cells) Neck Fundus Pawlina, Histology: A Text and Atlas; Alcian blue/PAS, x320 Fundic glands (Gastric glands) Produce about 2L/day, empty via gastric pit Gastric ‘juice’ consists of: Water Electrolytes HCl Pepsin Stem cell (generates Mucus all gland cells) Intrinsic factor Cell types in gland: Mucous cells Chief cells Parietal (oxyntic) cells Enteroendocrine cells Stem cells Junqueira’s Basic Histology Fundic (Gastric) gland : Mucous cell Two types based primarily on location: Surface mucous cell and Mucous neck cell Surface mucous cell: Columnar cell Lines inner surface of stomach and gastric pit Produces/secretes mucinogen (stains with PAS) mucus is thick, viscous, gel-like (cloudy) high concentration of bicarbonate and potassium Short lifespan (3-5 days) Mucous neck cell: Lines neck region of fundic gland Produces/secretes soluble mucous (i.e. clear), less mucinogen than surface mucous cell Secretion stimulated by vagus nerve Short lifespan (~6 days)  Gastric gland : Chief cells Protein secreting (enzymes, especially pepsinogen) Deep part of gland Basal cytoplasm is Basophilic due to abundant rER Apical zymogen granules are eosinophilic -often poorly stained 60-90day lifespan Cell and Tissue Biology, 6th ed Ross & Pawlina, Histology: A Text and Atlas Gastric gland : Parietal (oxyntic) cell Produce HCl and intrinsic factor HCl and intrinsic factor secretion activated by gastrin, histamine, & acetylcholine Intracellular canalicular system (where HCl produced) is continuous with gland lumen Large cells that stain with eosin (acidic dyes) Numerous microvilli Located in neck and deep part of gland ~150-200day lifespan Cell and Tissue Biology, 6th ed Gastric gland : Enteroendocrine cell Small cells that are ‘Open’ or ‘Closed’ cells Secrete peptides, polypeptide hormones and hormone-like regulating agents into the lamina propria or vasculature (not into gastric lumen) Chemoreceptors (‘Open’ cells) Cytoplasm often clear (or poorly stained) Names based on agent secreted and location: e.q. G cells, Gr cells, I cells, S cells, K cells, Mo cells 60-90day lifespan Junqueira’s Basic Histology; TEM, x4500 Ross & Pawlina, Histology: A Text and Atlas Enteroendocrine cells are present throughout the Stimulates GH secretion, Appetite & perception of hunger mucosa of the gastrointestinal tract Stimulates insulin relea Fundic glands CC, chief cells PC, parietal cells MNC, mucous neck cells SMC, surface mucous cells N, neck of fundic glands Pawlina, Histology: A Text and Atlas; H&E x320 Cardiac glands -tubular, tortuous, occasionally branched gland in mucosa -Present in cardia of stomach -Mainly mucus secretion Cell types mucous cells enteroendocrine cells Pawlina, Histology: A Text and Atlas; H&E x240 Pyloric glands -Tubular, coiled (near muscularis mucosae), branched gland in mucosa -’wide’ lumen -Present in pyloric antrum -Mainly mucus secretion Cell types mucous cells enteroendocrine cells a few parietal cells Pawlina, Histology: A Text and Atlas; H&E x120  Clinical application : Pernicious anemia Intrinsic factor complexes with vitamin B12 in the stomach and duodenum → absorption in the ileum Vitamin B12 deficiency due to malabsorption of vitamin B12, secondary to intrinsic factor deficiency Autoimmune, chronic gastritis/peptic ulcer disease, gastrectomy, long-term use histamine H2 receptor antagonists, diet All ages, but particularly those > 60 yo Common cause of megaloblastic anemia Develops slowly - 2 to 5 years to apparent clinical B12 deficiency Clinical application : Peptic ulcer Erosion of stomach mucosa 95% peptic ulcers are caused by a chronic infection of the gastric mucosa by Helicobacter pylori. Eventually antibodies against H. pylori bind to the gastric mucosa and cause damage to the mucosal cells Long term use of NSAIDs Some medications (corticosteroids, bisphosphonates, potassium chloride, and fluorouracil have been implicated) Complications if untreated: GI bleeding, perforation of stomach, gastric cancer Peptic ulcer ‘scars’ the stomach mucosa, decreasing the functionality of the mucosa which can contribute to Vitamin B12 deficiency Small intestine Mucosa: Villi Intestinal glands (crypts of Lieberkühn) GALT & Peyer’s patch Submucosa: Dense connective tissue Brunner’s gland Peyer’s patch Muscularis externa/propria: inner circular & outer longitudinal layer, myenteric plexus  Small intestine Duodenum → Jejunum → Ileum Duodenum & Jejunum - Pawlina, Histology: A Text and Atlas; H&E Small intestine : Mucosa Duodenum → Jejunum → Ileum Digestion and Absorption!!! Surface area increased by: Plicae circulares (circular folds) Villi Microvilli H&E, x22 x160 Pawlina, Histology: A Text and Atlas Small intestine : Mucosa Villi Intestinal glands (crypts of Lieberkühn) Epithelium – simple columnar -Enterocytes -Goblet cells -Paneth cells -Enteroendocrine cells -M cells (microfold cells) -Intermediate cells (stem cells) Lamina propria lacteal (lymphatic capillary) fenestrated capillaries GALT Ross & Pawlina, Histology: A Text and Atlas Peyer’s patches Muscularis mucosae - inner circular & outer longitudinal layer Small intestine : Mucosa Villi Intestinal glands (crypts of Lieberkühn) Epithelium – simple columnar -Enterocytes -Goblet cells -Paneth cells -Enteroendocrine cells -M cells (microfold cells) -Intermediate cells (stem cells) Lamina propria lacteal (lymphatic capillary) fenestrated capillaries GALT Peyer’s patches Muscularis mucosae - inner circular & outer longitudinal layer Enterocytes Columnar cells Primary function = Absorption, Intestinal absorptive cells Junqueira’s Basic Histology; PAS-hematoxylin, x500 Microvilli (striated border) Terminal web (contractile actin microfilaments in apical cytoplasm, attach to zonula adherens) Tight junctions Lateral plications (elaborate, flattened cytoplasmic processes) Also function - secrete glycoprotein enzymes into apical plasma membrane Ross & Pawlina, Histology: A Text and Atlas Goblet cells mucinogen granules Unicellular mucin-secreting gland PAS stains contents, H&E doesn’t Number increases duodenum → colon H&E Junqueira’s Basic Histology; PAS-hematoxylin, x250  Paneth cells Regulate normal bacterial flora in intestine - secrete α-defensins (antibacterial lysozyme) that digests cell wall of some bacteria Located at base of intestinal glands Strong eosin stain of secretory vesicles Cytoplasm is basophilic Ross & Pawlina, Histology: A Text and Atlas; H&E, x240; inset x680  M cells (Microfold cells) Epithelial cells that overlie lymphatic nodules (and Peyer’s patches) in lamina propria Microfolds (not microvilli) on apical surface Pocket-like recess basally Highly specialized ‘Antigen transporting cell’ Endocytose microorganisms (and macromolecules) from intestinal lumen, exocytose near lymphocytes/immune cells Ross & Pawlina, Histology: A Text and Atlas; SEM, x80 Intestinal glands “Crypts of Lieberkühn” Simple columnar epithelium Paneth cell Tubular structures that open at the base of villi Contain immune cells, including Paneth cells Major component of GALT (Gut- associated lymphoid tissue) Lamina propria Loose connective tissue Gut Associated Lymphatic Tissue (GALT) - loosely organized layer of lymphatic nodules, lymphocytes, macrophages, plasma cells, and eosinophils - immunologic barrier throughout the length of the gastrointestinal tract Lacteal - open ended lymphatic vessel Fenestrated capillaries x160 Ross & Pawlina, Histology: A Text and Atlas Submucosal layer : Brunner’s (submucosal) glands Branched tubular glands present in the submucosa of the duodenum Secrete enzymes and mucus Secretions are pH 8.1-9.3 (neutral & alkaline glycoproteins, and bicarbonate ions) Ross & Pawlina, Histology: A Text and Atlas H&E ×120 Junquiera; PAS & Hematoxylin Peyer’s patch Lymphatic nodule within lamina propria and submucosa Component of GALT (gut-associated lymphatic tissue) Immunologic barrier Prominent in ileum Large Intestine cecum, appendix, colon, rectum, anal canal Mucosa: Intestinal glands (crypts of Lieberkühn) GALT & Peyer’s patch Submucosa: Peyer’s patch Muscularis externa/propria: inner circular layer ileocecal valve/sphincter internal anal sphincter outer longitudinal layer teniae coli Ross & Pawlina, Histology: A Text and Atlas; 10x, H&E Large Intestine cecum, appendix, colon, rectum, anal canal Mucosa: Intestinal glands (crypts of Lieberkühn) GALT & Peyer’s patch Submucosa: Peyer’s patch Muscularis externa/propria: inner circular layer ileocecal valve/sphincter internal anal sphincter outer longitudinal layer teniae coli  Large Intestine : Mucosa Absorption of electrolytes and water, elimination of waste “smooth’ surface - No plicae circularis or villi present Junqueira’s Basic Histology; H&E x80 Large Intestine : Mucosa Simple columnar epithelium Columnar absorptive cells (Enterocytes) - reabsorb water and electrolytes, produce/secrete glycocalyx Goblet cells (more numerous than in small intestine) - secrete continuously Enteroendocrine cells Paneth cells are absent Intermediate cells (stem cells) Intestinal Glands (crypts of Lieberkühn) Lamina propria Collagen table (thick layer of collagen & proteoglycan) Pericryptal fibroblast sheath (at base of crypt) Lymphatic vessels are not present in the core of lamina propria GALT & Lymphatic nodules Muscularis mucosae Ross & Pawlina, Histology: A Text and Atlas; H&E; SEM, x140  Large Intestine cecum, appendix, colon, rectum, anal canal On outer surface: -Teniae coli thickened band of outer muscular layer on cecum & colon -Haustra coli sacculations between teniae coli of cecum & colon -Omental appendices fatty serosa projections on colon Ross & Pawlina, Histology: A Text and Atlas; 30x, H&E  Colon Clinical application : Diverticulosis Occurs in any part of colon, generally occurs in the left (descending and sigmoid) colon Approx. 2/3 adults develop, 32% 50-59yo 71% > 80yo Asymptomatic in ~75% https://doi.org/10.1038/ s41572-020-0153-5 Colon Clinical application : Diverticulosis (symptomatic uncomplicated diverticular disease)  Colon Clinical application : Diverticulosis Spot film from an air-contrast BE shows distortion of the colonic lumen. The luminal outpouchings image are diverticula, while the irregularly spaced infoldings of the wall image represent myochosis (circular muscle hypertrophy). Rectum → Anal canal Rectum mucosa, submucosa, and muscularis externa are like that of large intestine (no teniae coli) Ross & Pawlina, Histology: A Text and Atlas Anal canal : Mucosa Epithelium changes (simple columnar to stratified squamous) Lamina propria Muscularis mucosae and Intestinal glands disappear Simp Col E Strat Squam E, Strat Cub E, Strat Col E, Simp Col E Strat Squam E Ross & Pawlina, Histology: A Text and Atlas; H&E,10x (left); H&E, 200x (right) Anal canal : Mucosa Epithelium changes (simple columnar to stratified squamous) Lamina propria Muscularis mucosae and Intestinal glands disappear Ross & Pawlina, Histology: A Text and Atlas; H&E,10x; H&E, 40x (left image) 160x (right image)  Anal canal Submucosa anal glands (can extend into muscularis externa) – secrete mucus terminal branches of superior rectal artery rectal plexus (enlargements = internal hemorrhoids) Muscularis externa circular layer thickens to form internal anal sphincter Ross & Pawlina, Histology: A Text and Atlas; H&E,10x; H&E, 200x Thank you for your attention !